Prognostic Significance of the Hemoglobin A1c Level in Non-Diabetic Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis
Coronary artery disease (CAD) remains a significant global health concern, contributing to increased mortality rates worldwide. Percutaneous coronary intervention (PCI) has become a cornerstone in the management of acute myocardial infarction, significantly reducing periprocedural adverse events. Hemoglobin A1c (HbA1c), a well-established biomarker reflecting average blood glucose levels over the preceding 2 to 3 months, has been widely used in clinical practice. While elevated HbA1c levels are associated with increased risks of major adverse cardiac events (MACEs) in diabetic patients undergoing PCI, its prognostic significance in non-diabetic patients remains controversial. This meta-analysis aims to evaluate the association between HbA1c levels and adverse clinical outcomes in non-diabetic CAD patients post-PCI.
The study adhered to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and was registered on the PROSPERO database. A systematic search was conducted across PubMed, Embase, and The Cochrane Library from their inception to December 2018. The search strategy included terms related to PCI and HbA1c. Studies were eligible if they evaluated adverse clinical outcomes based on abnormal HbA1c levels in non-diabetic CAD patients who underwent PCI. The primary outcomes were long-term all-cause deaths and long-term MACEs, while the secondary outcome was short-term all-cause deaths. Data extraction and quality assessment were performed using the Newcastle Ottawa scale.
Six prospective cohort studies involving 10,721 patients met the inclusion criteria. The studies varied in terms of geographic location, sample size, follow-up duration, and HbA1c cut-off levels. Quality assessment revealed that five studies were of high quality, while one was sub-optimal. Baseline characteristics of the included patients, such as age, sex, body mass index (BMI), smoking status, hypertension, dyslipidemia, and family history of CAD, were also extracted.
The pooled analysis demonstrated that abnormal HbA1c levels were associated with an increased risk of long-term all-cause death (OR 1.39, 95% CI 1.16–1.68, P = 0.001, I² = 45%). Subgroup analysis indicated that in patients from the Netherlands, elevated HbA1c levels were associated with an 81% increased risk of death (OR 1.81, 95% CI 1.37–2.40, P < 0.001, I² = 0). However, in patients from other countries, such as Korea, Japan, and the USA, increased HbA1c levels did not significantly elevate the risk of death.
Three studies investigated the association between abnormal HbA1c levels and long-term MACEs. The overall analysis did not show a significant increase in long-term MACEs (OR 1.59, 95% CI 1.00–2.56, P = 0.050, I² = 72%). However, subgroup analysis revealed that when the abnormal HbA1c cut-off levels were between 6.0% and 6.5%, there was a significant increase in long-term MACE risk (OR 2.05, 95% CI 1.46–2.87, P < 0.001, I² = 0).
Three studies evaluated the impact of abnormal HbA1c levels on short-term all-cause deaths. The analysis did not find a statistically significant association (OR 1.16, 95% CI 0.88–1.54, P = 0.300, I² = 0). Sensitivity analyses confirmed the robustness of these findings.
The findings of this meta-analysis suggest that abnormal HbA1c levels are an independent risk factor for long-term adverse clinical events in non-diabetic CAD patients post-PCI. Specifically, HbA1c levels between 6.0% and 6.5% were associated with higher rates of long-term MACEs. These results align with recommendations from the International Expert Committee, which identifies HbA1c levels of 6.0% to 6.4% as indicative of an intermediate risk group, warranting intervention to prevent progression to diabetes and associated cardiovascular events.
Several mechanisms may explain the adverse impact of elevated HbA1c levels. Chronic hyperglycemia can induce vascular endothelial cell damage, leading to vasomotor dysfunction, excessive extracellular matrix formation, and increased cellular proliferation. Additionally, elevated HbA1c levels are associated with a higher cardiovascular risk profile, including hypertension and dyslipidemia, which may contribute to increased long-term mortality.
The study’s limitations include heterogeneity among the included studies in terms of inclusion criteria, HbA1c cut-off levels, follow-up duration, and concomitant treatments. Additionally, the observational nature of the studies precludes establishing causality. Despite these limitations, the findings underscore the importance of monitoring and controlling HbA1c levels in non-diabetic CAD patients undergoing PCI to improve long-term outcomes.
In conclusion, this meta-analysis highlights the prognostic significance of HbA1c levels in non-diabetic CAD patients post-PCI. Abnormal HbA1c levels, particularly between 6.0% and 6.5%, are associated with increased risks of long-term adverse clinical events. Cardiologists should consider HbA1c levels as a critical parameter in managing CAD patients, even in the absence of diabetes. Strict control of HbA1c levels may enhance patient survival and reduce the incidence of adverse outcomes. Further research, including prospective cohort studies with larger sample sizes and diverse populations, is necessary to validate these findings and explore regional disparities.
doi.org/10.1097/CM9.0000000000001029
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